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Click chemistry compared to thiol chemistry for the synthesis of site-selective glycoconjugate vaccines using CRM 197 as carrier protein.
- Source :
-
Glycoconjugate journal [Glycoconj J] 2020 Oct; Vol. 37 (5), pp. 611-622. Date of Electronic Publication: 2020 Jun 13. - Publication Year :
- 2020
-
Abstract
- Conjugation chemistry is one of the main parameters affecting immunogenicity of glycoconjugate vaccines and a rational approach toward a deeper understanding of their mechanism of action will greatly benefit from highly-defined and well-characterized structures. Herein, different conjugation methods were investigated with the aim of controlling glycosylation site and glycosylation density on the carrier protein. S. Typhimurium lipopolysaccharide O-Antigen and CRM <subscript>197</subscript> carrier protein were used as models. In particular, thiol and click chemistry were examined, both involving the linkage of the terminal reducing sugar unit of the O-Antigen chain to different amino acids on the carrier protein. Thiol chemistry allowed O-Antigen conjugation only when the carrier protein was activated on the lysines and with a relative high number of linkers, while click chemistry allowed conjugate generation even when just one position on the protein was activated and to both lysine and tyrosine sites. The study highlights click chemistry as a leading approach for the synthesis of well-defined glycoconjugates, useful to investigate the relationship between conjugate design and immune response.
- Subjects :
- Bacterial Proteins chemistry
Bacterial Proteins therapeutic use
Carrier Proteins therapeutic use
Click Chemistry
Glycoconjugates biosynthesis
Glycoconjugates immunology
Glycoconjugates therapeutic use
Humans
Lipopolysaccharides chemistry
Lipopolysaccharides immunology
O Antigens chemistry
O Antigens immunology
Salmonella Infections immunology
Salmonella Infections microbiology
Salmonella Infections prevention & control
Salmonella typhimurium chemistry
Salmonella typhimurium immunology
Salmonella typhimurium pathogenicity
Sulfhydryl Compounds therapeutic use
Vaccines biosynthesis
Vaccines immunology
Vaccines therapeutic use
Carrier Proteins chemistry
Glycoconjugates chemistry
Sulfhydryl Compounds chemistry
Vaccines chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1573-4986
- Volume :
- 37
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Glycoconjugate journal
- Publication Type :
- Academic Journal
- Accession number :
- 32535667
- Full Text :
- https://doi.org/10.1007/s10719-020-09930-2